[Genetic polymorphism in MDM2 is associated with susceptibility to colorectal cancer in a Chinese population].
OBJECTIVE
The tumor suppressor p53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage or oncogene activation. Mouse double minute 2 (MDM2) gene is a key negative regulator of p53 pathway and overexpressed in many cancers as oncoprotein. We have previously shown that genetic polymorphisms in the MDM2 promoter (309T --> G) and p53 coding region (72Arg --> Pro) are associated with susceptibility to esophageal and lung cancers. This study investigated the associations between these polymorphisms in p53 and MDM2 and risk of the occurrence and progression of colorectal cancer.


METHODS
Genotypes of 1000 Chinese colorectal cancer patients and 1300 controls were determined by PCR-based restriction fragment length polymorphism or tetra-primer amplification refractory mutation system-PCR. Associations with risk of colorectal cancer were estimated by unconditional logistic regression.


RESULTS
An increased colorectal cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.06, 95% confidence interval (CI) = 1.62-2.62] or TG (OR = 1.31, 95% CI = 1.06-1.62) genotype was observed compared with the TT genotype. No association was found between p53 polymorphism and risk of the cancer, with the ORs being 0.87 (95% CI = 0.68-1.11) for the Pro/Pro and 0. 85 (95% CI = 0.70-1.04) for the Arg/Pro genotype compared with the Arg/Arg genotype. However, combined analysis of MDM2 and p53 polymorphisms showed that compared with subjects carrying both MDM2 TT and p53 Arg/Arg genotypes, the OR for subjects carrying both MDM2 GG and p53 Pro/Pro genotypes was 2.75 (95% CI = 1.60-4.70), significantly higher than that for subjects carrying both MDM2 TT and p53 Pro/Pro genotypes (OR = 1.09, 95% CI = 0.63-1.88).


CONCLUSIONS
These results suggest that genetic polymorphism in MDM2 may be associated with susceptibility to colorectal cancer in a Chinese population.
Liu
Jun-Niao
JN
Department of Etiology and Carcinogenesis, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China.
Zhang
Xue-Mei
XM
Guo
Yong-Li
YL
Sun
Tong
T
Lin
Dong-Xin
DX
Wen
Tan
T
D000368:Aged; D044466:Asian People / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2